Conclusions
MD-MIX was able to counteract CRC development in mice under different dietary backgrounds through the regulation of apoptosis and gut microbiota.
Methods
Forty A/J male mice were randomly assigned into four feeding arms (10 mice/arm; LFD, LFD-MD-MIX, HFWD, HFWD-MD-MIX) to be treated with AOM. Ten mice were exposed to the diets alone (Healthy LFD and Healthy HFWD) to be used as control. Tumor incidence and multiplicity were evaluated at sacrifice. Mucosal fatty acid content and urinary phenolic compounds were assayed by mass spectrometry. Apoptosis was evaluated by TUNEL assay and gene expression markers. Cell proliferation was evaluated by Ki67 immunohistochemistry. Microbiota composition was assessed at different time points by 16S RNA sequencing.
Results
A tumor incidence of 100% was obtained in AOM-treated mice. The MD-MIX supplementation was able to reduce the number of colonic lesions in both LFD and HFWD-fed mice and to induce apoptosis, in particular in the LFD-MD-MIX arm. Moreover, a preventive effect on low-grade dysplasia and macroscopical lesions (>1 mm) development was found in HFWD-fed mice together with a regulation of the AOM-driven intestinal dysbiosis. Conclusions: MD-MIX was able to counteract CRC development in mice under different dietary backgrounds through the regulation of apoptosis and gut microbiota.